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Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels

Although both processes occur at similar rates, leukocyte extravasation from the blood circulation is well investigated, whereas intravasation into lymphatic vessels has hardly been studied. In contrast to a common assumption—that intra- and extravasation follow similar molecular principles—we previ...

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Detalles Bibliográficos
Autores principales: Pflicke, Holger, Sixt, Michael
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806476/
https://www.ncbi.nlm.nih.gov/pubmed/19995949
http://dx.doi.org/10.1084/jem.20091739
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author Pflicke, Holger
Sixt, Michael
author_facet Pflicke, Holger
Sixt, Michael
author_sort Pflicke, Holger
collection PubMed
description Although both processes occur at similar rates, leukocyte extravasation from the blood circulation is well investigated, whereas intravasation into lymphatic vessels has hardly been studied. In contrast to a common assumption—that intra- and extravasation follow similar molecular principles—we previously showed that lymphatic entry of dendritic cells (DCs) does not require integrin-mediated adhesive interactions. In this study, we demonstrate that DC-entry is also independent of pericellular proteolysis, raising the question of whether lymphatic vessels offer preexisting entry routes. We find that the perilymphatic basement membrane of initial lymphatic vessels is discontinuous and therefore leaves gaps for entering cells. Using a newly developed in situ live cell imaging approach that allows us to dynamically visualize the cells and their extracellular environment, we demonstrate that DCs enter through these discontinuities, which are transiently mechanically dilated by the passaging cells. We further show that penetration of the underlying lymphatic endothelial layer occurs through flap valves lacking continuous intercellular junctions. Together, we demonstrate free cellular communication between interstitium and lymphatic lumen.
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spelling pubmed-28064762010-06-21 Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels Pflicke, Holger Sixt, Michael J Exp Med Brief Definitive Report Although both processes occur at similar rates, leukocyte extravasation from the blood circulation is well investigated, whereas intravasation into lymphatic vessels has hardly been studied. In contrast to a common assumption—that intra- and extravasation follow similar molecular principles—we previously showed that lymphatic entry of dendritic cells (DCs) does not require integrin-mediated adhesive interactions. In this study, we demonstrate that DC-entry is also independent of pericellular proteolysis, raising the question of whether lymphatic vessels offer preexisting entry routes. We find that the perilymphatic basement membrane of initial lymphatic vessels is discontinuous and therefore leaves gaps for entering cells. Using a newly developed in situ live cell imaging approach that allows us to dynamically visualize the cells and their extracellular environment, we demonstrate that DCs enter through these discontinuities, which are transiently mechanically dilated by the passaging cells. We further show that penetration of the underlying lymphatic endothelial layer occurs through flap valves lacking continuous intercellular junctions. Together, we demonstrate free cellular communication between interstitium and lymphatic lumen. The Rockefeller University Press 2009-12-21 /pmc/articles/PMC2806476/ /pubmed/19995949 http://dx.doi.org/10.1084/jem.20091739 Text en © 2009 Pflicke and Sixt This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Pflicke, Holger
Sixt, Michael
Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
title Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
title_full Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
title_fullStr Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
title_full_unstemmed Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
title_short Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
title_sort preformed portals facilitate dendritic cell entry into afferent lymphatic vessels
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806476/
https://www.ncbi.nlm.nih.gov/pubmed/19995949
http://dx.doi.org/10.1084/jem.20091739
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